Seediscussions,stats,andauthorprofilesforthispublicationat:https://www.researchgate.net/publication/229640226

Protocolforthepreventionandtreatmentoforalsequelaeresultingfromheadandneckradiationtherapy

ArticleinCancer·October1992

DOI:10.1002/1097-0142(19921015)70:8<2171::AID-CNCR2820700827>3.0.CO;2-S

CITATIONS

65

READS

1,289

8authors,including:

JohanJansma

UniversityofGroningen

80PUBLICATIONS1,466CITATIONS

SEEPROFILE

FredKSpijkervet

UniversityofGroningen

75PUBLICATIONS2,258CITATIONS

SEEPROFILE

JanLNRoodenburg

UniversityofGroningen,UniversityMedicalCent…

255PUBLICATIONS5,243CITATIONS

SEEPROFILE

Allin-textreferencesunderlinedinbluearelinkedtopublicationsonResearchGate,

lettingyouaccessandreadthemimmediately.

Availablefrom:JanLNRoodenburg

Retrievedon:07October2016

2171

Protocol for the Prevention and Treatment of Oral Sequelae Resulting from Head and Neck Radiation Therapy Johan Jansma, D.D.S., Ph.D.,* Arjan Vissink, D.D.S., Ph.D.,t Fred K. L. Spijkervet, D.D.S., Ph.D.,* ]an L. N. Roodenburg, D.D.S., Ph.D.,* Arend K. Panders, D.M.D., Ph.D.,* Albert Vermey, M.D., Ph.D., F.A.C.S.,$ Ben G. Szab6, M.D., Ph.D.,§ and E. lohannes Is-Gravenmade, Ph.D. 1)

In addition to the desired antitumor effects, head and neck radiation therapy induces damage in normal tissues that may result in oral sequelae such as mucositis, hypo- salivation, radiation caries, taste loss, trismus, soft-tis- sue necrosis, and osteoradionecrosis. These sequelae may be dose-limiting and have a tremendous effect on the patient's quality of life, Current policies to prevent these sequelae primarily are based on clinical experience and show great diversity. A protocol for the prevention and treatment of oral sequelae resulting from head and neck radiation therapy, based on fundamental research and data derived from the literature, is presented. The proto- col is particularly applicable in centers with a dental team. This team should be involved at the time of initial diagnosis so that a successful preventive regimen is an integral part of the overall cancer treatment regimen. Cancer 1992; 70:2171-2180.

Key words: radiation therapy, side effect, prevention, treatment, hyposalivation, mucositis, xerostomia.

Radiation therapy plays an important role in the care of patients with head and neck cancer.' Because of the location of the primary tumor or the lymph node me- tastases, the salivary glands, oral cavity, and jaws often are included in the treatment portals.' As a result, changes induced by exposure to radiation occur in these tissues; these changes can lead to mucositis, hyposali-

From the Departments of *Oral and Maxillofacial Surgery, tRa- diobiology, $Surgery/Oncology, §Radiotherapy, and IINeurology, University Hospital Groningen, Groningen, The Netherlands.

The authors thank Dr. H. J. Guchelaar, Department of Phar- macy, University Hospital Groningen, for providing the composition of the sodium fluoride gel.

Address for reprints: Johan Jansma, D.D.S., Ph.D., Department of Oral and Maxillofacial Surgery, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.

Accepted for publication January 7, 1992.

vation, radiation caries, taste loss, trismus, soft-tissue necrosis and osteoradionecrosis (ORN).3,4 These oral se- quelae may cause substantial problems during and after radiation therapy and are major factors in determining the patient's quality of life. Acute exacerbation of focal infection, e.g., periapical and periodontal infection, and severe mucositis occasionally may necessitate an ad- justment or an interruption of the radiation treatment schedule. For these reasons, oral complications should be prevented or reduced to a m i n i m ~ m . ~

Most prevention procedures described in the litera- ture are based on clinical experience. The result is a great diversity in treatment p ~ l i c i e s ~ - ~ and in the pre- ventive approach in daily practice." Many publications in this field deal only with one sequela. Overall proto- cols are rare or are extremely concise. In this report, a new overall protocol for the prevention and treatment of oral sequelae resulting from head and neck radiation therapy is proposed. The scientific basis of this protocol is formed by the hyposalivation studies of Vissink," the mucositis studies of Spijkervet," and the radiation car- ies studies of Jansma,I3 supplemented with data de- rived from the literature. The protocol is especially ap- plicable in centers operating with a dental team (ideally consisting of an oral and maxillofacial surgeon, a hospi- tal dentist, and an oral hygienist) that is devoted to the wide range of preventive and treatment measures.

Prevention and Treatment

The protocol can be divided into three phases of patient care, namely before radiation exposure (Table l), dur- ing radiation exposure (Table 2), and after radiation ex- posure (Table 3). The primary issues of patient care be- fore radiation exposure are screening, consequential treatment, explication, patient motivation, and initia- tion of preventive measures. Management during radia-

2172 CANCER October 15, 1992, Volume 70, No. 8

Table 1. Care of Patient Before Radiation Therapy

Physical and radiographic examination Dentition (caries, restorations, calculus, vitality) Periodontiurn (bleeding index, pocket depth, furcation

Oral hygiene (plaque, bleeding index, denture hygiene) Dental awareness and motivation Oral mucosa and alveolar process (infection, irritation fibroma,

hyperplasia, exostosis) Dentures (fit of partial or full dentures) Mouth opening (on indication) Radiographic examination

involvement)

Panoramic radiograph (intraoral radiographs when indicated) Detection of foci (periapical infections, periodontal disease,

unerupted or partially erupted teeth, residual root tips, cysts) Treatment and prophylaxis

Extraction of nonsalvageable teeth and surgical removal of foci (alveolotomy, primary wound closure, 3 weeks of wound healing)

Dental prophylaxis (polishing, scaling, root planing, curettage) Restorative dental procedures (restorations, endodontics) Dentures (correction of ill-fitting dentures, no soft lining) Initiation of preventive regimen

Plaque removal (tooth brushing, interdental plaque removal) Topical fluoride (application of neutral 1% sodium fluoride gel

every second day, custom-made fluoride carriers) Oral rinses (salt-soda rinses at least 8-10 times daily) Selective oral flora elimination (lozenges containing polymyxin

E, tobramycin, and amphotericin B four times daily) Denture wearing discouraged after the start of radiation

therapy

therapy, when indicated)

dietitian)

Trismus prevention (exercises from the start of radiation

Nutritional advises (instructions, counseling; ideally by a

tion therapy is characterized by prevention and treat- ment of acute complications induced by radiation expo- sure and comprehensive counseling. After radiation

Table 2. Care of Patient During Radiation Treatment

Standard oral hygiene and preventive care Plaque removal (tooth brushing, interdental plaque removal) Topical fluoride (1 YO sodium fluoride gel application every second

Oral rinses (salt-soda rinses at least 8-10 times daily) Selective oral flora elimination (lozenges containing polymyxin E,

tobramycin, and amphotericin B four times daily) Discouraging denture wearing Nutritional counseling (monitoring body weight, instructions,

Visits with dental team at least once a week

Professional daily spraying with saline (mucositis, insufficient

0.1% chlorhexidine rinses (plaque removal) Sucralfate suspensions or viscous lidocaine (pain relief) Saliva substitutes (relief of oral dryness) Trismus prevention (exercises, measuring mouth opening)

day)

artificial feeding)

Additional measures (on indication)

oral rinsing)

Table 3. Care of Patient After Radiation Therapy

FOIIOW-UP Frequent dental checkups, preferably coordinated with oncology

recall Examination, prevention, and treatment

Oral mucosa Treatment of mucositis or recall mucositis (salt-soda rinses,

lozenges containing polymyxin E, tobramycin, and amphotericin 8)

Waiting period of 3 months before (re)placement of dentures Careful examination of oral mucosa and denture hygiene

Clinical assessment of salivary secretion (inspection,

Relief of oral dryness (gustatory and tactile sialogogues, oral

Oral dryness

stimulation)

rinses, saliva substitutes, mucin-containing lozenges)

Evaluation and reinforcement of oral hygiene regimen 1 % sodium fluoride gel application every second day lifelong;

Physical and radiographic examination (caries, calculus,

Restorative and prophylactic dental procedures as needed Extractions and other surgical procedures after radiation

Dentition and periodontiurn

reduction guided by salivary function and oral hygiene

vitality, pocket depth)

therapy under high-dose antibiotic coverage; prophylactic hyperbaric oxygen treatment on indication

Trismus prevention Exercise program until 3-6 months after radiation therapy Physiotherapy (on indication)

Noncariogenic, nonirritating diet Adiustments for hvDosalivation and taste disturbances

Nutritional counseling

therapy, the prevention and treatment of chronic and late complications in conjunction with close follow-up are the main issues of patient care. The protocol is sche- matically depicted in Figure 1.

Care of Patients before Radiation Therapy

All dentulous and edentulous patients of whom parts of the jaws, the major salivary glands, or the oral cavity will be located in the field of radiation should receive a comprehensive dental evaluation before radiation ther- apy (Table 1). The objectives of the evaluation are:

identification of risk factors for the development of oral complications, in particular those that may inter- fere with the radiation treatment, such as exacerba- tion of periapical and periodontal infections;

performance of necessary treatment and prophylaxis to reduce the likelihood of oral complications during and after radiation therapy;

initiation of a comprehensive preventive care program.

To maximize the effect of this screening, adequate time for dental treatment, fabrication of fluoride car-

2173 Oral Sequelae Resulting from Head and Neck Radiation Therapy/Jansma et al.

I I I -

prevention of caries sod periodontal disease I

I

f 1 rmlryliaa 4

I I T apicll- I

I I I I

trisrnus prevention 1 - I .lo.itoriql- I I f*Bsda 1- ' # m b = v ! iphvrbbnW ! I

I

I

I

I I I I

I

I [ I I I

I

I I !

I I

Figure 1. The primary concerns of I patient care before, during, and after 1 I radiation therapy. I

PRE-IRRADIATION PHASE IRRADIATION PHASE (6.7 wks) POST-IRRADIATION PHASE (lifelong)

examination and

treafment Plan

dental prophylaxis

restorative can

riers, and wound healing after extractions or other sur- gical procedures is needed. That is why the initial ap- pointment for dental evaluation must be made shortly after initial cancer diagnosis and at least 3 weeks before the onset of radiation therapy.

Physical and Radiographic Examination

Dentition. The patient's dentition should be exam- ined. Teeth must be checked for carious lesions, defec- tive restorations, sources of potential irritation of the oral mucosa and periodontium, e g , sharp or rough fill- ings and calculus, and vitality of the pulp.

Periodontium. The periodontal status is a major dental consideration and should be thoroughly screened by measuring pocket depths and assessment of furcation involvement.

Oral hygiene. The level of oral hygiene should be checked carefully. Plaque and bleeding indices are helpful parameters. The hygiene of partial or full den- tures also should be checked.

Dental awareness and motivation. The patient's dental awareness is an important consideration in the dental evaluation. The protocol aims at preventing or reducing oral sequelae, some of which may have life- long duration (hyposalivation) or risk (radiation caries or ORN). Thus, patients must possess the motivation and physical ability to maintain dentition properly and

I i !

I I l i ,

to comply completely with the prescribed oral hygiene and preventive regimen. Oral hygiene and dental status may be indicative of what can be expected in this re- spect.

Oral mucosa and alveolar process. The oral mu- cosa and alveolar process must be checked, especially for conditions that may interfere with future denture wearing, such as ulcerations, fibromas, irritation hyper- plasia, bony spicules, and tori.

Dentures. The fit of dentures should be checked because ill-fitting dentures are a potential source of irri- tation and trauma of the mucosal surfaces exposed to radiation and the underlying bone.

Mouth opening. The maximum mouth opening (interarch distance) should be recorded before radiation therapy when development of trismus is anticipated, i.e., when masticatory muscles or other soft tissues surrounding the temporomandibular joint are included in the field of radiation, particularly in instances of tu- mor invasion and surgical resections before radiation exposure in these regions.'r6

Oral flora. Gram-negative bacilli and their endo- toxins were found to play a significant role in the devel- opment of serious forms of muc~sitis. '~ Thus, all pa- tients for whom a substantial part of the oral mucosa will be located in the field of radiation exposure should receive selective oral flora elimination. Because of the long-term administration of antibiotics and antimycot- ics, it is preferable to take baseline cultures, with the

2174 CANCER October 15,1992, Volume 70, No. 8

oral washing method described by Spijkervet et al.15 in these patients.

Radiographic examination. In addition to the physical examination, radiographic screening must be done for all patients. A panoramic radiograph, supple- mented by intraoral radiographs when necessary, is most suitable for the detection of risk factors such as periodontal and periapical infections, cysts, third molar pathology, unerupted or partially erupted teeth, and residual root tips.

Treatment and Prophylaxis

After the oral examination is performed, a dental treat- ment plan is made. In principle, maintenance of as many teeth as possible, prevention of the necessity of extractions after radiation therapy, and prevention of acute complications that may interfere with the radia- tion treatment are the primary goals. All teeth with a questionable prognosis should be extracted before radi- ation therapy. For the decision of extraction before radi- ation therapy or maintenance of teeth, several factors are of importance. They include the patient's motiva- tion and ability to comply with the preventive regimen. A lack of motivation on the part of the patient should lead to a decision to extract teeth before radiation ther- apy. Radiation exposure type, field, and dose also are important. The risk of development of ORN is maximal after cumulative doses to the bone that exceed 65 Gy; this is particularly true of the molar region of the man- dible.'6,'7

Extractions before radiation therapy and surgical removal of other foci. Extraction or surgical removal of teeth usually is indicated in these circumstances:

advanced carious lesions with questionable pulpal sta-

extensive periapical lesions; moderate to advanced periodontal disease (pocket-

depth in excess of 5 mm), especially with advanced bone loss, mobility, or furcation involvement;

residual root tips not fully covered by alveolar bone or showing radiolucency;

impacted or incompletely erupted teeth that are not fully covered by alveolar bone or that are in contact with the oral environment;

tus or pulpal involvement;

teeth in close proximity to tumor.

Deeply impacted teeth that are covered completely by bone and mucosa usually can be left without risk of late problems.','

Extractions and surgical removal of residual root tips, impacted teeth, and other foci such as cysts should be performed atraumatically with regard to tissue han-

dling. Alveolotomy (lowering and smoothing the bony alveolar margins) and primary wound closure are neces- sary to speed healing and to eliminate sharp ridges and bony spicules, which may project into the overlying soft t iss~es. '~ This is particularly important for prosthetic considerations because negligible bone remodeling can be expected after radiation therapy.

Nonvital teeth located in the field of radiation without periapical radiolucency and not causing com- plaints can be treated endodontically. With mandibular molars, apicoectomies with orthograde filling are pre- ferred because of the high ORN risk in this region and the frequent problems with endodontic treatment on multirooted teeth. Teeth with small or moderate periapi- cal granulomas without periodontal involvement that are important for oral functioning or rehabilitation should be treated with apicoectomies. Extraction is in- dicated for extensive periapical radiolucency, simulta- neous periodontal involvement, and lack of function.

Irritation hyperplasia, fibromas, bony spicules, and tori should be removed when they interfere with den- ture wearing or construction of new dentures.

Adequate time for wound healing before radiation therapy is essential because it is related to the develop- ment of ORN." Healing times of 3 weeks generally are considered safe and should be the rule." Routinely anti- biotic coverage is not recommended because there is no evidence that antibiotics influence healing in the ab- sence of infection.' Careful examination of the extrac- tion sites must be performed before radiation treat- ment. With the examination, the clinician can deter- mine the healing period required for the patient.

Dental prophylaxis and restorative care. It is cru- cial to bring the periodontium into optimal condition before radiation therapy because of the lowered poten- tial for healing afterward." Thorough oral hygiene pro- cedures, including scaling and polishing or subgingival root planing and curettage, should be performed as needed. Overhanging restorations should be recon- toured or renewed to remove plaque and food retention factors. Extensive scaling and subgingival curettage should be completed at least 3 weeks before radiation therapy to allow for sufficient wound healing. With ad- vanced periodontal disease (pocket-depth of more than 5 mm), extraction is inevitable because of the risk of ORN and the lack of time for sufficient periodontal treatment, such as flap operations.

Restorative care, including restoration of carious le- sions and replacement of defective restorations, should be performed as needed.

Ill-fitting partial or full dentures should be corrected. Temporary soft liners exhibit increased fric- tion because of the hyposalivation induced by radiation exposure. In addition, they may easily become colon-

2175 Oral Sequelae Resulting from Head and Neck Radiation Therapyllansma et at.

ized with yeasts because of their porosity. Thus, soft liners are contraindicated in patients with head and neck radiation exposure. Construction of new dentures should be postponed until 3 months after radiation therapy.

Initiation of a New Preventive Regimen

A protocol aimed at prevention and relief of mucositis, prevention of hyposalivation-related dental caries and periodontal disease (and thus ORN), relief of oral dry- ness, and prevention of weight loss and trismus must be instituted in all patients at risk. Because most preven- tive measures must be continued throughout the pa- tient’s life, patient and family education, counseling, and motivation are critical to the success of the preven- tive regimen.

Oral hygiene. Patients must be instructed about an effective daily plaque removal. Instructions regarding the use of a soft toothbrush with a fluoride-containing toothpaste and the Bass-technique of sulcular brushing are needed. The use of dental floss or soft wooden toothpicks is imperative for removal of interdental plaque. Interproximal brushes, irrigating devices, and plaque-disclosing tablets can be helpful. Proper oral hygiene cannot be overemphasized, and patients ef- forts should be evaluated before radiation therapy. In- structions regarding denture hygiene should be pro- vided.

Caries prevention and topical fluorides. Al- though oral hygiene measures are imperative in the prevention of radiation caries, it has been shown that oral hygiene alone is inadequate as a safeguard against radiation ~aries.’l-‘~ Topical fluoride applications are needed to prevent radiation caries. A neutral 1% so- dium fluoride gel, self-applied every second day using custom-made carriers, in conjunction with strict oral hygiene measures is an effective preventive regimen.23 Acidulated gels are not indicated in patients receiving radiation exposure because such gels may lead to signifi- cant decalcification without sufficient remineralization potential in the presence of hyposalivation. They also may cause mucosal irritation with burning pain, ery- thema, and ~lcerat ion.~,~ In addition, sodium fluoride preparations are preferred to stannous fluoride because the latter has unpleasant side effects, such as bad taste, sensitivity of teeth and gingivae, and staining of arrested lesion^.'^

At the initial dental appointment, impressions should be taken to fabricate flexible fluoride carriers that extend approximately 3 mm beyond the free mar- gin of gingivae and fit the teeth closely to allow for adequate fluoride coverage. They must be made before radiation therapy. After the patient has thoroughly

brushed and flossed, the 1 YO sodium fluoride (NaF) gel should be applied for 5-10 minutes every second day, preferably immediately before bedtime. The carriers must not be overfilled; a few drops of gel are sufficient. After removing the carriers, the patient spits out excess gel without rinsing and must refrain from drinking, brushing, or eating for 30 minutes. Patients with an extreme gag reflex can apply the fluoride gel using a toothbrush instead of a carrier.

In patients with large metal restorations or crowns located in the field of radiation, carriers of double thick- ness can be fabricated; these carriers must be worn dur- ing radiation exposure to prevent tissue injury by scat- tering, thereby preventing localized mucositis, espe- cially of the buccal mucosa.

Oral rinse instructions. For relief of oral discom- fort during radiation therapy, cleansing agents are rec- ommended to reduce mucosal irritation, to remove thickened secretions and debris from mucosa and den- tition, and to moisture and lubricate the m u c o ~ a . ~ ~ When radiation therapy begins, the patient should rinse the mouth at least eight to ten times a day for 1 minute with a salt-soda solution (one liter lukewarm water with one teaspoon each of NaCl and Na,CO,). This solution is preferred because of its ability to dissolve mucus and loosen debris.

Daily professional spraying of the oral cavity with saline using a spraying device (Heberle spray set, La- meris, Ultrecht, The Netherlands) is a good supplement to thorough mechanical cleansing, Professional spray- ing should be performed, especially for patients who have serious complaints because of mucositis or who are unable to rinse sufficiently.

Saliva substitutes. Symptomatic relief of oral dry- ness also can be accomplished with saliva substitutes. Although mucin-containing substitutes seem to be more eff ecti~e,’~,’’ carboxymethylcellulose (CMC)- containing substitutes may be beneficial. The success of using saliva substitutes is strictly dependent on the in- structions delivered with their prescription. The patient should moisten the oral cavity abundantly with an at- omizer, spread the substitute over the entire oral cavity and swallow or expectorate the surplus. As soon as the sensation of dryness returns, the treatment should be repeated, The substitute can be used ad libitum. Saliva substitutes can be diluted with water for patients who find the agents’ viscosity objectionable. Difficulty in speech and swallowing and nocturnal oral discomfort are the most useful indices for their use.

Selective oral flora elimination. Selective elimina- tion of gram-negative bacilli from the oral flora during radiation therapy has resulted in prevention of the more severe stages of mucositis (pseudomembranes and ulcer^).'^ Four times daily administration of 1-g loz-

2176 CANCER October 15,1992, Volume 70, No. 8

enges containing 2 mg polymyxin E, 1.8 mg tobramy- cin, and 10 mg amphotericin B (PTA) is prescribed to all patients for whom a substantial part of the oral mucosa will be located in the field of radiation. The PTA loz- enges should be used from the onset of radiation ther-

aged. Adequacy of oral intake should be monitored by regularly measuring the body weight.

Patient care during ~ ~ d j ~ ~ j ~ ~ Treatment

apy, during its full course, and until mucositis signs

esis of mucositis, the preventive administration of the topical antifungal amphotericin B is indicated in this population to prevent yeast stomatitis.''

Denture wearing. Dentures, especially ill-fitting ones, may cause mucosal irritation during radiation therapy; this irritation may aggravate mucosal pain and mucositis. The policy must be to discourage the wearing of partial and full dentures from the start of radiation therapy in all patients in whom a substantial area of the

Maintenance of optimal oral hygiene, preventive mea-

cerns during the radiation treatment period (Table 2). During this time, patients must have checkups by the radiation therapist and must be screened by a member of the dental team at least once a week. During these screening visits, the oral situation, the oral hygiene, and preventive measures should be checked, evaluated, and if necessary reinforced. Additional measures can be ini- tiated, depending on the oral status and complaints.

have disappeared. t' the pathogen- sures, and relief of oral discomfort are the primary con-

oral mucosa is located in the field of radiation and who will receive a curative radiation dose. An exception must be made for patients wearing resection prostheses and obturators, which are needed for closure of the sur- gical defect and for prevention of tissue retraction into this defect.

Trismus prevention. Prevention of trismus, rather than its treatment, is a desirable objective. As soon as radiation therapy begins, patients at risk of trismus need daily exercises, such as properly instructed stretching, to maintain maximum opening and jaw mo- bility. The additional use of tongue blades or rubber stops of increasing size is helpful and stimulating be- cause they act as measuring devices. Dynamic bite openers2 that contain springs and bands and are de- signed to restretch muscles also can be used for preven- tion in pediatric patients.

Nutritional instructions. The oral intake of food during radiation therapy may be impeded because of taste loss, changes in amount and viscosity of saliva, and pain, caused by mucositis, on eating and swallow- ing.3*29 Resulting weight loss leads to weakness, inactiv- ity, discouragement, and susceptibility to infection.

Nutritional counseling and dietary instructions are important for minimizing weight loss and preventing the necessity of nasogastric feeding. All patients should receive dietary instructions before radiation therapy, ideally by a dietitian. Foods high in sucrose enhance the cariogenic activity and should be avoided, as should spicy and acidic foods that are intolerable to the sensi- tive oral mucosa. To ease mastication in association with hyposalivation and mucositis, patients are encour- aged to increase fluid intake and to eat moistened foods served at room temperature. Small frequent feedings are recommended when appetite is poor and when swallowing is difficult. Tobacco and alcohol use, which contributes to mucosal irritation, is strongly discour-

Oral Hygiene

If tooth brushing has become painful because of muco- sitis, one or more of the following additional measures should be initiated: professional cleansing of the denti- tion by an oral hygienist during the weekly visits; 0.1% aqueous chlorhexidine rinses three to four times daily for additional plaque control; and rinses with a topical anesthetic, such as viscous lidocaine, shortly before tooth brushing to relief pain from brushing. Patients also may be advised to soften their toothbrush with hot tap water before use.

Topical fluorides. The neutral 1 Yo NaF gel must be applied every second day by the patient using the cus- tom-made carriers.

Mucositis prevention and therapy. Patients should rinse their mouths at least eight to ten times daily with the salt-soda solution and use the PTA 102- enges four times daily during the full course of radia- tion therapy. When patients have difficulties in dissolv- ing the PTA lozenges because of hyposalivation, they should be instructed to moisten their mouths and re- move the remnants of the lozenge after 30 minutes of sucking. To monitor oral flora, surveillance cultures should be taken weekly in all patients using PTA loz- e n g e ~ . ~ ~

Denture wearing is discouraged after radiation ther- apy begins. With large metal restorations or crowns lo- cated in the field of radiation, patients should wear their double-thickness carriers during radiation expo- sure. In patients with severe complaints caused by mu- cositis or who are unable to rinse sufficiently, additional daily spraying with saline should be performed by the oral hygienist or nursing staff. Once mucositis has de- veloped, a sucralfate suspension (1 g/15 ml) can be prescribed for pain relief as a rinsing agent.30

Oral Sequelae Resulting from Head and Neck Radiation Therapy/Jansma et al . 2177

Relief of oral dryness. Oral rinses with salt and soda are important for mechanical cleansing during ra- diation therapy but also sufficiently relieve oral dryness in most patients. If they do not, their frequency can be increased, and patients can be encouraged to increase fluid intake, provided the beverages are noncariogenic and nonirritating to the oral mucosa. Saliva substitutes also can be prescribed.

Trismus prevention. All patients at risk of having trismus should perform the instructed exercises. When the interarch distance decreases, the exercise program should be intensified, occasionally in combination with physiotherapy, to regain the lost interarch distance.

Nutritional counseling. When weight loss exceeds 1 kg per week, enriched dietary supplements are recom- mended. Nasogastric feeding is indicated when a loss of 10% of the body weight before radiation exposure is observed in the third or fourth week of radiation therapy.31

Care of the Patient after Radiation Therapy

In addition to relief of oral dryness and discomfort, the primary purpose of the protocol after radiation therapy is prevention of radiation caries, periodontal disease, extractions, and thus ORN (Table 3). Oral hygiene must be maintained at a high level indefinitely in all patients, whereas topical fluoride applications must be contin- ued lifelong in most dentulous patients. The risk of noncompliance increases with time after radiation ther- apy. Patients must be placed on a regular dental recall schedule and be judiciously followed up for the rest of their lives. This is necessary to check, evaluate, and rein- force the oral hygiene regimen, to encourage patients to adhere to the protocol, and to counsel a possible reduc- tion in fluoride usage. As a general rule, follow-up visits should be weekly during the first month, every three months during the next year, and less frequently there- after; however, schedules may differ, depending on the level of oral hygiene, degree of hyposalivation, and whether the patient is dentulous or edentulous. For rea- sons of efficacy, the follow-up visits should be com- bined with the oncology recall. The patient’s dentist, when instructed properly, can play an important role in the period after radiation therapy by caring for the pa- tient during these visits or working with the dental team.

Oral Mucosa

Mucositis. Frequent rinsing with salt-soda solu- tions, the use of PTA lozenges, and other preventive or therapeutic measures should be continued until muco-

sitis signs have disappeared. With recall mucositis, the basic regimen of mucositis prevention should be rein- stituted.

Dentures. The oral mucosa that has been exposed to radiation is vulnerable and easily damaged, a condi- tion that is aggravated by hypo~alivation.~’ Trauma to the edentulous alveolar ridge may result in soft-tissue necrosis and lead to ORN. Dentures are considered to be a potential source of such trauma.33 Timing of their (re)placement is controversial. Factors such as compli- ance, amount and consistency of saliva, presence of re- cent extraction sites, and experience in wearing den- tures before radiation therapy are important decisive parameters. Our guideline is to wait 3 months before (re)placing dentures so that initial mucosal changes have subsided. This waiting period is extended to 6 months for patients who had extractions before radia- tion therapy in the field of the radiation-exposed area. An exception is made for resection prostheses.

After dentures are replaced or constructed and placed, preferably by an experienced hospital dentist, the patient should remove the dentures at night. Den- ture hygiene should be stressed to the patient. Because of increased friction, porosity, and accumulation of de- bris, soft liners are not indicated in this group of pa- tients.

If irritation develops, dentures must be removed immediately and the mouth must be examined by the dental team. Stringent continuous care after radiation therapy is essential in denture-wearing patients. The fit of the dentures should be checked every year by the family dentist or by the dental team.

Oral Dryness

The degree of hyposalivation and return of salivary gland function primarily depend on the total radiation dose and the volume of salivary gland tissue located in the field of radiation, whereas the initial salivary flow also is of i m p ~ r t a n c e . ~ ~ , ~ ~ Studies have indicated that there is almost no recovery of salivary flow when the major salivary glands are situated in the treatment por- tals and receive a cumulative radiation dose in excess of 40 Gy.21,35 In many patients with head and neck cancer, cumulative radiation dosages of 60-70 Gy are adminis- tered to one or more of the salivary glands, so hyposali- vation is irreversible in most instances. This has a tre- mendous effect on caries challenge and quality of life for the patient.

Relief of oral dryness. The management of hypo- salivation involves a combination of two strategies: stimulation of residual capacity of salivary glands and relief of oral dryness. Most patients experience improve-

2178 CANCER October 25, 2992, Volume 70, No. 8

ment in symptoms from frequent moistening of the mouth by drinking or rinsing with water, tea, salt-soda solutions, extracts of camomile, and home remedies, such as old brown ale and blueberry juice. Additional treatment of oral dryness should be instituted, depend- ing on the subjective complaints of the patient. During each follow-up visit, questions regarding such com- plaints should be asked and verified by clinical assess- ment. For this assessment of the degree of hyposaliva- tion, a few parameters are of interest, including appear- ance of the oral mucosa (dry, atrophic, fissured), aspect of the oral fluid (more viscous), and level of salivary secretion in rest and after stimulation.

When stimulation of salivary glands shows residual capacity, sialogogues can be used to relieve oral dry- ness. Good results can be obtained with gustatory and tactile sialogogues, such as sugar-free chewing gum and acidulated sweets. However, the latter can be used only in limited amounts because they often are intolerable to the mucosa exposed to radiation. Although their useful- ness seems limited because of their potential side ef- fects, pharmacologic sialogogues such as pilocarpine have been reported to be successful in stimulating addi- tional ~ e c r e t i o n . ~ ~ " ~

Saliva substitutes that contain mucin or CMC also can be prescribed; the mucin-containing substitutes seem to be the most e f f e ~ t i v e . ~ ~ , ~ ~ Construction of a sa- liva substitute reservoir in a denture has been helpful in a number of selected patient^,^^,^^ but application of the substitute with an atomizer, provided it is used correctly, is sufficient in most patients. Recently, prom- ising results were obtained with the use of mucin-con- taining lozenges in the treatment of oral symptoms of xero~tomia.~" These lozenges are particularly useful when combined with mucin-containing saliva substi- tutes.

Den ti tion

Oral hygiene. Patients must maintain a high level of oral hygiene throughout their lives. Oral hygiene should be checked carefully during follow-up visits. If necessary, patients should be motivated and oral hy- giene measures reinforced.

Topical fluoride. Topical fluoride application must be continued as long as hyposalivation exists, which is lifelong in most pa t ien t~ .~ l ,~ l Although some authors mention the possibility of reducing the frequency of fluoride application, depending on such factors as level of oral hygiene and salivary flow rate,4,7 and despite that reduction of the application frequency is common in Dutch radiation therapy institutes," no studies re- garding fluoride reduction have been reported to justify

this measure. Because of the irreversibility of hyposali- vation in many patients and the aggressiveness and high cariogenity of the xerostomic oral environment as observed in in situ s t ~ d i e s , ~ ' , ~ ~ , ~ ~ the application of a 1% neutral NaF gel every second day must be continued throughout the patient's life. Reduction of the applica- tion frequency is justified only in patients with objec- tive indications of recovery of salivary flow in combina- tion with a high level of oral hygiene. In this respect, one must remember that in approximately one third of the xerostomic patients, there is no correlation between objective and subjective mouth dryness.43 In addition, reduction must be guided by close follow-up for evalua- tion and possibility of individual adjustment and quick intervention. Should initial carious lesions appear, dura- tion and frequency of fluoride applications can be in- creased temporarily for remineralization and caries arrest. Topical fluoride should be applied at least twice a year. Applications can be performed by a dentist or an oral hygienist during follow-up visits.

Physical and radiographic examination. The pa- tient's dentition should be checked carefully for carious lesions and calculus. Periapical films and bitewings should be made to examine teeth previously treated by endodontics or apicoectomies and for canes detection. The periodontium should be thoroughly screened by measuring pocket depths.

Restorative and prophylactic care. If carious le- sions develop, they should be treated immediately be- cause of the rapid progression in xerostomic patients. Teeth with nonvital pulps located in jaw segments ex- posed to radiation should be treated endodontically, rather than by apicoectomy, because of the amount of wounding. Removal of calculus by scaling and root planing and curettage also should be performed to opti- mize periodontal health. Chronic periodontal disease may induce ORN and should be prevented.

Extractions after radiation therapy. Extraction of teeth from jaw segments exposed to radiation is a signif- icant factor predisposing to ORN.I7 Screening before radiation, treatment, and the institution of a regimen are aimed at preventing the necessity of these extrac- tions. The necessity for extraction after radiation ther- apy usually is caused by insufficient screening before radiation therapy and patient noncompliance with the regimen. Several investigators have shown that the time elapsed between radiation therapy and tooth re- moval has little direct bearing on the occurrence of ORN,44 whereas others have reported the risk to in- crease with time." However, it seems that limited ex- tractions can be done successfully when necessary, pro- vided adequate preventive measures are taken.

Extractions are performed with careful soft-tissue

Oral Sequelae Resulting from Head and Neck Radiation Therapy/Jansma et al . 2179

handling, alveolotomies, and primary wound closure. This is important to speed healing and for future pros- thetic considerations. Prophylactic high-dose, broad spectrum antibiotic coverage, eg, cephalosporins, is started a few days before extraction and continued for 2 weeks to prevent wound infection. Preventive hyper- baric oxygen treatment has been proven to be more beneficial than antibiotic prophylaxis in preventing ORN45 but is not widely available in most countries. Prophylactic hyperbaric oxygen treatment must be used in patients who require extractions or who experi- enced excessive wounding in segments previously ex- posed to radiation and who are considered to be at the highest risk of having ORN, ie, patients with cumula- tive radiation doses in excess of 65 Gy to mandibular segments and who have risk factors such as impeded blood supply caused by tumor operation, abuse of alco- hol and tobacco, and compromised general health. Wound healing of extractions performed after radiation therapy should be checked regularly.

hospital dentist, and an oral hygienist, that is devoted to covering the wide range of preventive and treatment measures. This team should be involved at the time of initial cancer diagnosis so that a preventive regimen is an integral part of the overall cancer treatment regimen. The role of a family dentist before and during radiation therapy probably is limited because of the complexity of oral screening and oral care, the possible complica- tions during radiation therapy, and the fact that most family dentists rarely are confronted with this type of patient. In our opinion, the family dentist's role is lim- ited to the care of patients with uncomplicated disease after they have received radiation therapy.

With the implementation of new radiation expo- sure schedules in head and neck radiation therapy (more early side effects in association with hyperfrac- tionation and accelerated treatment) and the increasing number of aged dentulous patients, adequate preven- tion is a matter of increasing importance.

References Trismus Prevention

Trismus (with muscular cause) may develop as late as 3-6 months after completion of radiation Thus, patients at risk of having trismus are advised to continue exercises during this period and should be as- sisted by physiotherapy when indicated. The interarch distance should be measured during follow-up visits and compared with the distance as determined before radiation exposure.

Nutritional Counseling

After mucositis signs have subsided, patients generally may return to a regular diet. Because of the hyposaliva- tion induced by radiation therapy and its related taste disturbances, foods may have to be moistened and served with liquids for an indefinite period of time, and smell and taste may have to be adapted to individual needs.

Epilogue

A protocol for the prevention and reduction of most oral sequelae resulting from head and neck radiation therapy has been proposed; the scientific basis is formed by the hyposalivation studies of Vissink," the mucositis studies of Spijkervet," and the radiation car- ies studies of Jansma,13 in combination with data de- rived from the literature. The protocol is especially ap- plicable in centers operating with a dental team, which ideally consists of an oral and maxillofacial surgeon, a

1.

2.

3.

4.

5 .

6 .

7.

8.

9.

10.

11.

12.

13.

Rothwell BR. Prevention and treatment of the orofacial compli- cations of radiotherapy. J A m Dent Assoc 1987; 114:316-22. Engelmeier RL, King GE. Complications of head and neck radia- tion therapy and their management. J Prusthet Dent 1983;

Beumer 1, Curtis TA, Hamson RE. Radiation therapy of the oral cavity: sequelae and management, part 1. Head Neck Surg 1979; 1:301-12. Beumer J, Curtis TA, Harrison RE. Radiation therapy of the oral cavity: sequelae and management, part 2. Head Neck Surg 1979;

National Institutes of Health Consensus Development Panel. Consensus statement: oral complications of cancer therapies. NCI Monugr 1990; 9:3-8. Ritchie JR, Brown JR, Guerra LR, Mason G. Dental care for the irradiated cancer patient. Quintessence Int 1985; 12:837-42. Wright WE, Haller M, Harlow SA, Pizzo PA. An oral disease prevention program for patients receiving radiation and chemo- therapy. J Am Dent Assoc 1985; 110:43-7. Lockhart PB. Oral complications of radiation therapy. In: Peter- son DE, Elias EG, Sonis ST, eds. Head and neck management of the cancer patient. Boston: Martinus Nijhoff, 1986:429-49. Lowe 0. Pretreatment dental assessment and management of patients undergoing head and neck irradiation. Clin Prevent Den- tistry 1986; 8:24-30. Jansma J, Vissink A, Bouma J, Panders AK, Vermey A, Graven- made EJ. A survey of prevention and treatment regimens of oral sequelae resulting from head and neck radiotherapy used in Dutch radiotherapy institutes. Znt Radiat Oncul B i d Phys. In press. Vissink A. Xerostomia: development, properties and application of a mucin containing saliva substitute [thesis]. Groningen, The Netherlands: University of Groningen, 1985. Spijkervet FKL. Irradiation mucositis and oral flora: reduction of mucositis by selective elimination of oral flora [thesis]. Gronin- gen, The Netherlands: University of Groningen, 1989. Jansma J. Oral sequelae resulting from head and neck radiother-

49~514-22.

1~392-408.

2180 CANCER October 15, 1992, Volume 70, No. 8

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

apy: course, prevention and management of radiation caries and other oral complications [thesis]. Groningen, The Netherlands: University of Groningen, 1991. Spijkervet FKL, van Saene HKF, van Saene JJM, Panders AK, Vermey A, Mehta DM, et al. Effect of selective elimination of oral flora on mucositis in irradiated head and neck cancer pa- tients. J Surg Oncol 1991; 46:167-73. Spijkervet FKL, van Saene HKF, Panders AK, Vermey A. Coloni- sation index of the oral cavity: a novel technique for monitoring colonisation defence. Microb Ecol Health Dis 1989; 2:145-51. Murray CG, Herson J, Daly TE, Zimmerman S. Radiation necro- sis of the mandible: a 10-year study: Part I. factors influencing the onset of necrosis. Int J Radiat Oncol Biol Phys 1980; 6:543-8. Friedman RB. Osteoradionecrosis: causes and prevention. NCI Monogr 1990; 9:145-9. Beumer J, Harrison R, Sanders B, Kurrasch M. Preradiation den- tal extractions and the incidence of bone necrosis. Head Neck Surg 1983; 5:514-21. Marx RE, Johnson RP. Studies in the radiobiology of osteora- dionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol 1987; 64:379-90. Silverman 5, Chierici G. Radiation therapy of oral carcinoma: I. effects on oral tissues and management of the periodontium. 1 Periodontol 1965; 36:478-84. Dreizen 5, Brown LR, Daly TE, Drane JB. Prevention of xerosto- mia-related dental caries in irradiated cancer patient. J Dent Res

Jansma J, Vissink A, 's-Gravenmade EJ, de Josselin de long E, Jongebloed WL, Retief DH. A model to investigate xerostomia- related dental caries. Caries Res 1988; 22:357-61. Jansma J, Vissink A, 's-Gravenmade EJ, Visch LL, Fidler V, Re- tief DH. In vivo study on the prevention of postradiation caries. Caries Res 1989; 23:172-8. Myers RE, Mitchell DL. Fluoride for the head and neck radiation patient. Milit Med 1988; 153:411-3. Miaskowski C. Management of mucositis during therapy. NCI Monogr 1990; 9:95-8. Vissink A, 's-Gravenmade EJ, Panders AK, Petersen JK, Visch LL, Schaub RMH. A clinical comparison between commercially available mucin- and CMC-containing saliva substitutes. Int J Oral Surg 1983; 12:232-8. Visch LL, 's-Gravenmade EJ, Schaub RMH, van Putten WLJ, Vissink A. A double-blind crossover trial of CMC- and mucin- containing saliva substitutes. Int Oral Maxillofac Surg 1986;

Martin MV, Al-Tikriti U, Bramley PA. Yeast flora of the mouth and skin during and after irradiation for oral and laryngeal cancer. 1 Med Microbiol 1981; 14:457-67. Donaldson SS. Nutritional consequences of radiotherapy. Cancer Res 1977; 37:2407-13.

1977; 56:99-104.

15:395-400.

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

Barker G, Loftus L, Cuddy P, Barker B. The effects of sucralfate suspension and diphenhydramine syrup plus kaolin-pectin on radiotherapy-induced mucositis. Oral Surg Oral Med Oral Pathol

Johnson HC. Nutritional care of cancer patients receiving radio- therapy. In: Fletcher GH, ed. Textbook of radiotherapy. 3rd ed. Philadelphia: Lea & Febiger, 1980:92-102. Baker DG. The radiobiological basis for tissue reactions in the oral cavity following therapeutic X-irradiation. Arch Otolaryngol

Toljanic JA, Saunders VW. Radiation therapy and management of the irradiated patient. 1 Prosthet Dent 1984; 52:852-8. Mira JG, Fullerton GD, Wescott WB. Correlation between initial salivary flow rate and radiation dose in production of xerosto- mia. Acta Radio1 Oncol 1982; 21:151-4. Liu RP, Fleming TJ, Toth BB, Keene HJ. Salivary flow rates in patients with head and neck cancer 0.5 to 25 years after radio- therapy. Oral Surg Oral Med Oral Pathol 1990; 70:724-9. Fox PC, van der Ven PF, Baum BJ, Mandel D. Pilocarpine for the treatment of xerostomia associated with salivary gland dysfunc- tion. Oral Surg Oral Med Oral Pathol 1986; 61:243-5. Greenspan D, Daniels TE. Effectiveness of pilocarpine in postra- diation xerostomia. Camer 1987; 59:1123-5. Vissink A, 's-Gravenmade EJ, Panders AK, Olthof A, Venney A, Hussman MC, et al. Artificial saliva reservoirs. 1 Prosthet Dent 1984; 52:710-5. Vissink A, Huisman MC, 's-Gravenmade EJ. Construction of an artificial saliva reservoir in an existing maxillary denture. Prosthet Dent 1986; 56:70-4. 's-Gravenmade EJ, Vissink A. Mucin-containing lozenges in the treatment of intra-oral problems associated with Sjogren's syn- drome: a double-blind cross-over study in 42 patients. Oral Surg Oral Med Oral Pathol. In press. Horiot JC, Schraub S, Bone MC, Bain Y, Ramadier J, Chaplain G, et al. Dental preservation in patients irradiated for head and neck tumors: a 10-year experience with topical fluoride and a randomized trial between two fluoridation methods. Radiother Oncol 1983; 1:77-82. Jansma J, Vissink A, Youngblood WL, Retrief DH, 's-Graven- made EJ. A SEM study of natural and induced radiation caries. A m 1 Dent. In press. Vissink A, Panders AK, 's-Gravenmade EJ, Vermey A. The causes and consequences of hyposalivation. Ear Nose Throat 1

Beumer J, Harrison R, Sanders B, Kurrasch M. Postradiation den- tal extractions: a review of the literature and a report of 72 epi- sodes. Head Neck Surg 1983; 6:581-6. Mam RE, Johnson RP, Kline SN. Prevention of osteoradionecro- sis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin. 1 A m Dent Assoc 1985; 11 1:49-54.

1991; 71:288-93.

1982; 108:21-4.

1988; 67:166-76.